Endogenous Presenilin-1 Targets to Endocytic Rather Than Biosynthetic Compartments
Abstract
Presenilin-1 (PS1), which is linked to familial Alzheimer's disease, participates in the proteolytic processing of Notch and amyloid-beta precursor protein (APP) by an unknown mechanism. Reports of PS1 localization to the endoplasmic reticulum (ER) and Golgi apparatus have focused attention on the early biosynthetic pathway as the site of PS1 function. However, it is unclear how Notch cleavage and APP processing events which occur at or near the cell surface are influenced by PS1. In contrast to some earlier studies, examination of endogenously expressed PS1 in PC12 cells by subcellular fractionation and immunofluorescence microscopy revealed a distribution distinct from that of ER and Golgi markers. Rather, PS1 colocalized with transferrin receptor, a marker for early endosomes. In addition, electron microscopic examination of intact vesicles immunoisolated with PS1 antibodies allowed visualization of endocytic tracer in endosomes. These findings identify an early endosomal pool of PS1 and suggest alternative mechanisms for PS1 interactions with APP and Notch.
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The mature cleaved form of presenilin1 (active component of γ-secretase) is present in fractions enriched with the recycling endosomal marker transferrin receptor (TfnR) after subcellular fractionation, and this enrichment is correlated with high levels of colocalization of these two proteins.
“In agreement with this evidence, it has been shown that the mature cleaved form of presenilin1 (active component of γ-secretase) is present in fractions enriched with the recycling endosomal marker transferring receptor (TfnR) after subcellular fractionation, and this enrichment is correlated with high levels of colocalization of these two proteins [72].”
From Sorting nexin 17 regulates ApoER2 recycling and reelin signaling (2014) · cites this paper as [72]
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Sorting nexin 17 regulates ApoER2 recycling and reelin signaling
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- Authors
- Lah, J. J., & Levey, A. I.
- Affiliations
- Emory University (US)
- Venue
- Molecular and Cellular Neuroscience
- Publisher
- Elsevier BV
- Published
- 2000-08
- Volume
- 16
- Issue
- 2
- Pages
- 111-126
- ISSN
- 1044-7431 (ISSN-L)
- OpenAlex
- W1990189498
- Cited by
- 84
- References
- 5
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 2 · 2012: 5
- FWCI
- 4.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (NS01902, K08NS001902)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
- Keywords
- presenilin 1, Alzheimer's disease, Notch cleavage, endosomes, endocytic pathway, subcellular localization, transferrin receptor, PC12 cells, Golgi apparatus, endoplasmic reticulum
- MeSH terms
- Animals, Antibodies, Monoclonal, Cell Compartmentation, Endoplasmic Reticulum, Fluorescent Antibody Technique, Golgi Apparatus, Membrane Proteins, Microscopy, Electron, Neurons, Endosomes, Subcellular Fractions, Amyloid beta-Peptides, PC12 Cells, Rats, Receptors, Notch, Presenilin-1
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